Frailty Trajectories and Incident Stroke Risk in People Aged 50 and Older: A Three-Cohort Prospective Analysis

Introduction: Frailty is dynamic in later life, yet prospective evidence linking frailty trajectories to incident stroke across diverse populations is limited. To investigate the association between frailty trajectories and incident stroke risk in adults aged 50 years and older using data from three nationally representative cohorts. Methods: We analyzed harmonized data from three longitudinal cohorts: the English Longitudinal Study of Ageing (ELSA), the Health and Retirement Study (HRS), and the China Health and Retirement Longitudinal Study (CHARLS). Frailty was assessed using a deficit-accumulation frailty index at each wave. Frailty trajectories were identified using latent class mixed models, which classified participants into three groups: Low, Moderate, and Increasing-to-high. Incident stroke was ascertained through self-reported physician diagnosis. Associations between frailty trajectory group membership and incident stroke were assessed using Cox proportional hazards models in the pooled dataset, stratified by cohort, and adjusted for demographic, socioeconomic, lifestyle, and laboratory covariates. Results: Among 19,666 participants, the median follow-up was 7.5 years (IQR 7.0–8.0), and 1,131 (5.8%) incident strokes occurred. In the fully adjusted model, compared with the Low trajectory group, the Moderate trajectory group had a significantly higher risk of incident stroke (HR 2.05, 95% CI 1.73–2.43), as did the Increasing-to-high group (HR 3.51, 95% CI 2.99–4.12) (both P < 0.001). Cohort-specific analyses showed consistent directions of association. Conclusion: Frailty trajectories were strongly associated with incident stroke risk across three prospective cohorts. Longitudinal frailty monitoring may help identify individuals at elevated stroke risk and inform targeted prevention strategies.